Hypothalamic-pituitary-adrenal (HPA) axis functioning as predictor of antidepressant response–Meta-analysis

Background/Aims: A meta-analysis was performed to determine the likelihood of hypothalamic-pituitary-adrenal (HPA) axis suppression following short-term cutaneous treatment of atopic dermatitis with topical corticosteroids (TCS) in pediatric patients. Methods: All published pediatric clinical trials evaluating TCS use with pre- and post-treatment HPA axis assessment by cosyntropin stimulation testing were included. Results: Of 128 eligible trials, 12 were selected for meta-analysis with a total of 522 participants. There were 20 observed cases of HPA axis suppression (3.8%, 95% CI 2.4–5.8). The percentage of HPA axis suppression with low- (classes 6–7), medium- (classes 3–5) and high-potency (classes 1–2) TCS use was 2% (3 of 148 patients, 95% CI 0.7–5.8), 3.1% (7 of 223 patients, 95% CI 1.5–6.3), and 6.6% (10 of 151 patients, 95% CI 3.6–11.8), respectively. Conclusion: There is a low rate of reversible HPA axis suppression with the use of mid- to low-potency TCS compared to more potent formulations. In pediatric clinical practice, the limited use of mid- to low-potency TCS is rarely associated with clinically significant adrenal insufficiency or adrenal crisis. In the absence of signs and symptoms of adrenal insufficiency, there is little need to test the HPA axis of these patients.

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Adulthood trauma and HPA-axis functioning in healthy subjects and PTSD patients: A meta-analysis

Psychoneuroendocrinology ◽

10.1016/j.psyneuen.2011.07.003 ◽

2012 ◽

Vol 37 (3) ◽

pp. 317-331 ◽

Cited By ~ 103

Author(s):

Ellen R. Klaassens ◽

Erik J. Giltay ◽

Pim Cuijpers ◽

Tineke van Veen ◽

Frans G. Zitman

Keyword(s):

Hpa Axis ◽

Healthy Subjects ◽

Meta Analysis ◽

Hpa Axis Functioning

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Hypothalamic-Pituitary-Adrenal (HPA) axis functioning in relation to body fat distribution

Clinical Endocrinology ◽

10.1111/j.1365-2265.2009.03712.x ◽

2009 ◽

Vol 72 (6) ◽

pp. 738-743 ◽

Cited By ~ 22

Author(s):

Femke Rutters ◽

Arie G. Nieuwenhuizen ◽

Sofie G. T. Lemmens ◽

Jurriaan M. Born ◽

Margriet S. Westerterp-Plantenga

Keyword(s):

Body Fat ◽

Hpa Axis ◽

Fat Distribution ◽

Body Fat Distribution ◽

Hypothalamic Pituitary Adrenal ◽

Hpa Axis Functioning

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Loneliness Mediates the Relationship Between Early Life Stress and Perceived Stress but not Hypothalamic–Pituitary–Adrenal Axis Functioning

Frontiers in Psychology ◽

10.3389/fpsyg.2021.647265 ◽

2021 ◽

Vol 12 ◽

Author(s):

Isabel Crespo-Sanmiguel ◽

Mariola Zapater-Fajarí ◽

Matias M. Pulopulos ◽

Vanesa Hidalgo ◽

Alicia Salvador

Keyword(s):

Perceived Stress ◽

Hpa Axis ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Childhood And Adolescence ◽

Diurnal Cortisol ◽

Hypothalamic Pituitary Adrenal ◽

Hpa Axis Functioning ◽

The Relationship

Many authors have proposed that early life stress (ELS) provokes a dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and contributes negatively to the management of stress in adulthood. However, these associations have not always been observed, making it necessary to include new factors that could explain the different results found. In this regard, people with ELS experiences report less social support during adulthood, suggesting that loneliness could be a mediating factor. Thus, our aims were to investigate whether ELS was related to both perceived stress and diurnal HPA axis activity, and whether loneliness mediates these relationships, in a community sample (N=187, 18–55years old). Fourteen cortisol samples were collected on two non-consecutive days to obtain the overall diurnal cortisol, diurnal cortisol slope, and bedtime levels. Additionally, ELS was assessed with the Risky Families Questionnaire (RFQ) and the Recalled Childhood and Adolescence Perceived Stress (ReCAPS) measure. Results revealed that ELS was associated with perceived stress, but not HPA axis functioning, and loneliness mediated the relationship between ELS and perceived stress, but not between ELS and HPA axis functioning. Similar results were found for both ELS questionnaires, suggesting that the ReCAPS is an adequate tool. These results highlight the importance of loneliness in understanding the long-term effects of ELS, and they indicate different effects of ELS on subjective and physiological stress indicators.

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A systematic review and meta-analysis of Synacthen tests for assessing hypothalamic-pituitary-adrenal insufficiency in children

Archives of Disease in Childhood ◽

10.1136/archdischild-2015-308925 ◽

2016 ◽

Vol 101 (9) ◽

pp. 847-853 ◽

Cited By ~ 15

Author(s):

Sze May Ng ◽

Juliana Chizo Agwu ◽

Kerry Dwan

Keyword(s):

Systematic Review ◽

Adrenal Insufficiency ◽

Hpa Axis ◽

Standard Dose ◽

Controlled Trial ◽

Meta Analysis ◽

Characteristic Curve ◽

Positive Likelihood Ratio ◽

Hypothalamic Pituitary Adrenal ◽

Synacthen Test

BackgroundThe diagnostic value of tests used in assessing hypothalamic-pituitary-adrenal axis (HPA) in children remains controversial.DesignA systematic review and meta-analysis with receiver-operated-characteristic curve was undertaken to assess the diagnostic values of conventional standard dose 250 μg tetracosactrin (ACTH), short Synacthen test (SSST) and/or low-dose Synacthen test (LDSST) in the assessment of HPA insufficiency in children. Studies eligible for inclusion were any study that compared the use of the LDSST and/or SSST in the assessment of central adrenal insufficiency in children compared with reference standard test.ResultsThere were no randomised trials found. SSST resulted in higher specificity and positive likelihood ratio than LDSST. The LDSST had a higher sensitivity (86% vs 61%) but a lower specificity (88% vs 99%) than the SSST, but there was high heterogeneity from the LDSST studies with various doses of Synacthen used.ConclusionsLack of standardisation of assays and protocols with regard to timing, frequency and dose has resulted in diagnostic inaccuracies. There is no clear evidence to indicate that LDSST is superior to SSST in the assessment of HPA axis in children. The choice of either SSST or LDSST should be individualised based on clinical judgement for each patient. This systematic review has identified the need for a well-designed, adequately powered, randomised controlled trial on the use of diagnostic tests used in assessing HPA axis in children.

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Urbanicity, hypothalamic-pituitary-adrenal axis functioning, and behavioral and emotional problems in children: a path analysis

BMC Psychology ◽

10.1186/s40359-019-0364-2 ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

B. E. Evans ◽

J. van der Ende ◽

K. Greaves-Lord ◽

A. C. Huizink ◽

R. Beijers ◽

...

Keyword(s):

Mental Health ◽

Socioeconomic Status ◽

Hpa Axis ◽

Indirect Effects ◽

Urban Areas ◽

Mental Health Problems ◽

Health Problems ◽

Family Socioeconomic Status ◽

Hypothalamic Pituitary Adrenal ◽

Hpa Axis Functioning

Abstract Background Urbanization is steadily increasing worldwide. Previous research indicated a higher incidence of mental health problems in more urban areas, however, very little is known regarding potential mechanisms underlying this association. We examined whether urbanicity was associated with mental health problems in children directly, and indirectly via hypothalamic-pituitary-adrenal (HPA)-axis functioning. Methods Utilizing data from two independent samples of children we examined the effects of current urbanicity (n = 306, ages seven to 12 years) and early childhood urbanicity (n = 141, followed from birth through age 7 years). Children’s mothers reported on their mental health problems and their family’s socioeconomic status. Salivary cortisol samples were collected during a psychosocial stress procedure to assess HPA axis reactivity to stress, and at home to assess basal HPA axis functioning. Neighborhood-level urbanicity and socioeconomic conditions were extracted from Statistics Netherlands. Path models were estimated using a bootstrapping procedure to detect indirect effects. Results We found no evidence for a direct effect of urbanicity on mental health problems, nor were there indirect effects of urbanicity through HPA axis functioning. Furthermore, we did not find evidence for an effect of urbanicity on HPA axis functioning or effects of HPA axis functioning on mental health problems. Conclusions Possibly, the effects of urbanicity on HPA axis functioning and mental health do not manifest until adolescence. An alternative explanation is a buffering effect of high family socioeconomic status as the majority of children were from families with an average or high socioeconomic status. Further studies remain necessary to conclude that urbanicity does not affect children’s mental health via HPA axis functioning.

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Sex differences in early-life programming of the hypothalamic–pituitary–adrenal axis in humans suggest increased vulnerability in females: a systematic review

Journal of Developmental Origins of Health and Disease ◽

10.1017/s204017441600074x ◽

2017 ◽

Vol 8 (2) ◽

pp. 244-255 ◽

Cited By ~ 70

Author(s):

T. Carpenter ◽

S. M. Grecian ◽

R. M. Reynolds

Keyword(s):

Systematic Review ◽

Sex Differences ◽

Birth Weight ◽

Low Birth Weight ◽

Hpa Axis ◽

Early Life ◽

Meta Analysis ◽

Later Life ◽

Cortisol Secretion ◽

Hypothalamic Pituitary Adrenal

Fetal glucocorticoid overexposure is a key mechanism linking early development with later-life disease. In humans, low birth weight associates with increased fasting cortisol, hypothalamic–pituitary–adrenal (HPA) axis reactivity, and with cardiovascular risk and cognitive decline. As there are sex differences in these adult diseases, we hypothesized that there may be sex differences in programming of the HPA axis in response to prenatal stressors. We conducted a systematic review following Meta-Analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We searched Embase, MEDLINE and Web of Science from inception to 31 October 2016. We included studies related to sex differences, prenatal exposures and HPA axis. We excluded studies investigating specific disease states. The 23 included studies investigated the consequences of low birth weight, preterm birth and maternal stressors of asthma, psychosocial stress and glucocorticoid medications on HPA axis outcomes of placental glucocorticoid biology and offspring HPA axis function in early life and later life. Female offspring exposed to stressors had increased HPA axis reactivity compared with males. Furthermore, the female placenta increased its permeability to maternal glucocorticoids following maternal stress with changes in the expression of 11β-hydroxysteroid dehydrogenase enzymes in response to maternal glucocorticoid exposure or asthma. Among males there was some evidence of altered diurnal cortisol secretion. We conclude that although there is some evidence of male vulnerability leading to altered diurnal cortisol secretion, the female HPA axis is more vulnerable to programming, particularly in terms of its reactivity; this suggests a mechanism underlying sex differences in later-life diseases.

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